Non-covalent interactions in anisole-(CO2)n (n = 1, 2) complexes.

Non-covalent interactions are ubiquitous and represent a very important binding motif. The direct experimental measurement of binding energies in complexes has been elusive for a long time despite its importance, for instance, for understanding and predicting the structure of bio-macromolecules. Here, we report a combined experimental and computational analysis on the 1 : 1 and 1 : 2 clusters formed by anisole (methoxybenzene) and carbon dioxide molecules. We have obtained a detailed description of the interaction between CO2 and anisole. This system represents quite a challenging test for the presently available experimental and theoretical methods for the characterization of weakly bound molecular complexes. The results, evaluated in the framework of previous studies on anisole clusters, show a very good agreement between experimental and theoretical data. A comparison of the experimental and computational data enabled the binding energy values of the 1 : 1 and 1 : 2 clusters to be determined in the ground electronic state of the neutral and cation complex and in the first excited singlet state of the neutral complex. In addition, it was possible to adduce the presence of different 1 : 1+ conformers, prepared by direct ionization of the 1 : 1 complex or by dissociative ionization of the 1 : 2 complex.

Binding energies of the π-stacked anisole dimer: new molecular beam-laser spectroscopy experiments and CCSD(T) calculations.

Among noncovalent interactions, π-π stacking is a very important binding motif governed mainly by London dispersion. Despite its importance, for instance, for the structure of bio-macromolecules, the direct experimental measurement of binding energies in π-π stacked complexes has been elusive for a long time. Only recently, an experimental value for the binding energy of the anisole dimer was presented, determined by velocity mapping ion imaging in a two-photon resonant ionisation molecular beam experiment. However, in that paper, a discrepancy was already noted between the obtained experimental value and a theoretical estimate. Here, we present an accurate recalculation of the binding energy based on the combination of the CCSD(T)/CBS interaction energy and a DFT-D3 vibrational analysis. This proves unambiguously that the previously reported experimental value is too high and a new series of measurements with a different, more sensitive apparatus was performed. The new experimental value of 1800±100 cm(-1) (5.15±0.29 kcal mol(-1)) is close to the present theoretical prediction of 5.04±0.40 kcal mol(-1). Additional calculations of the properties of the cationic and excited states involved in the photodissociation of the dimer were used to identify and rationalise the difficulties encountered in the experimental work.

Structure and energetics of the anisole-Ar(n) (n = 1, 2, 3) complexes: high-resolution resonant two-photon and threshold ionization experiments, and quantum chemical calculations.

We present a concerted experimental and theoretical study of the anisole···Arn complexes with n = 1-3. Experimentally, anisole was seeded into a pulsed supersonic argon jet producing a molecular beam. Resonant two-photon, two-colour ionisation (R2PI) spectra of anisole···Arn complexes with n = 1-3 were obtained. Also, the photodissociation of the (1 : 1) cluster was probed synchronously by - Zero Electron Kinetic Energy Photoelectron Spectroscopy (ZEKE) - and - Mass Resolved Threshold Ionization (MATI) - measuring electrons and ions obtained from pulsed field ionization of high-n Rydberg states upon two-colour laser excitation. The experimental results are compared to quantum chemical calculations at the DFT-D3 (B-LYP/def2-QZVP level with Grimme's D3 dispersion correction) level. Structure and energetics due to microsolvation effects by the direct interaction of the argon atoms with the π-system were evaluated. The experimental binding energy of the 1 : 1 cluster is finally compared to computational results; in the S0 ground state the theoretical value based on the "gold standard" CCSD(T)/CBS calculations lies within the error bars of the observed value. In the excited state the agreement between theory and experiment is not so spectacular but relative values of observed dissociation energies (D0) in the ground and excited states and of calculated ones agree well.

[Role of stem cells in the pathogenesis of chronic obstructive pulmonary disease and of pulmonary emphysema]. / Ruolo delle cellule staminali nella patogenesi della broncopneumopatia cronica ostruttiva e dell'enfisema polmonare.

There are only few human translational studies performed in the area of stem cell research in patients with chronic obstructive pulmonary disease (COPD) and/or pulmonary emphysema. Before progress to clinical trials with stem cells we believe that more human translational studies are necessaries, otherwise the clinical rationale would be solely based on limited in vitro and animal studies. In the future, stem cell therapy could be a treatment for this disease. Currently, stem cell therapy is still to be considered as an area of active research, lacking a strong rationale for performing clinical trials in COPD. Although stem cells would be likely to represent a heterogeneous population of cells, the different cell subsets and their importance in the pathogenesis of the different clinical phenotypes need to be fully characterised before progressing to clinical trials. Moreover, the potential side effects of the stem cell therapy are often underestimated. We should not ignore that some of the most deadly neoplasms are arising from stem cells.

Noncovalent interactions in the gas phase: the anisole-phenol complex.

The present paper reports on an integrated spectroscopic study of the anisole-phenol complex in a molecular beam environment. Combining REMPI and HR-LIF spectroscopy experimental data with density functional computations (TD-M05-2X/M05-2X//N07D) and first principle spectra simulations, it was possible to locate the band origin of the S(1) ← S(0) electronic transition and determine the equilibrium structure of the complex, both in the S(0) and S(1) electronic states. Experimental and computational evidence indicates that the observed band origin is due to an electronic transition localized on the phenol frame, while it was not possible to localize experimentally another band origin due to the electronic transition localized on the anisole molecule. The observed structure of the complex is stabilized by a hydrogen bond between the phenol, acting as a proton donor, and the anisole molecule, acting as an acceptor through the lone pairs of the oxygen atom. A secondary interaction involving the hydrogen atoms of the anisole methyl group and the π electron system of the phenol molecule stabilizes the complex in a nonplanar configuration. Additional insights about the landscapes of the potential energy surfaces governing the ground and first excited electronic states of the anisole-phenol complex, with the issuing implications on the system photodynamic, can be extracted from the combined experimental and computational studies.

A role for phosphoinositol 3-kinase delta in the impairment of glucocorticoid responsiveness in patients with chronic obstructive pulmonary disease.

BACKGROUND: Glucocorticoid function is markedly impaired in the lungs of patients with chronic obstructive pulmonary disease (COPD). This reduction in glucocorticoid sensitivity might be due to an oxidant-mediated increase in phosphoinositol 3-kinase (PI3K) delta signaling. OBJECTIVE: We sought to determine the role of PI3Kdelta in the reduced glucocorticoid responsiveness in patients with COPD. METHODS: Peripheral lung tissue was obtained from 24 patients with COPD, 20 age-matched smokers with normal lung function, and 13 nonsmokers. Peripheral blood monocytes were isolated from 9 patients with COPD and 7 age-matched smokers with normal lung function and from healthy volunteers. RESULTS: The expressions of PI3Kdelta and Akt phosphorylation were increased in macrophages from patients with COPD compared with those from control groups of age-matched smokers and nonsmokers. In vitro oxidative stress induced phosphorylation of Akt in monocytes and macrophages, which was abolished by means of selective inhibition of PI3Kdelta but not PI3Kgamma. Dexamethasone was less effective at repressing LPS-induced GM-CSF and CXC motif chemokine 8 release in blood monocytes from patients with COPD compared with age-matched smokers. This reduced sensitivity was reversed by inhibition of PI3Kdelta but not PI3Kgamma. CONCLUSION: PI3Kdelta expression and signaling is increased in the lungs of patients with COPD. Selective inhibition of PI3Kdelta might restore glucocorticoid function in patients with COPD and might therefore present a potential therapeutic target.

Towards Understanding Photodegradation Pathways in Lignins: The Role of Intramolecular Hydrogen Bonding in Excited States.

The photoinduced dynamics of the lignin building blocks syringol, guaiacol, and phenol were studied using time-resolved ion yield spectroscopy and velocity map ion imaging. Following irradiation of syringol and guaiacol with a broad-band femtosecond ultraviolet laser pulse, a coherent superposition of out-of-plane OH torsion and/or OMe torsion/flapping motions is created in the first excited (1)ππ* (S1) state, resulting in a vibrational wavepacket, which is probed by virtue of a dramatic nonplanar → planar geometry change upon photoionization from S1 to the ground state of the cation (D0). Any similar quantum beat pattern is absent in phenol. In syringol, the nonplanar geometry in S1 is pronounced enough to reduce the degree of intramolecular H bonding (between OH and OMe groups), enabling H atom elimination from the OH group. For guaiacol, H bonding is preserved after excitation, despite the nonplanar geometry in S1, and prevents O-H bond fission. This behavior affects the propensities for forming undesired phenoxyl radical sites in these three lignin chromophores and provides important insight into their relative "photostabilities" within the larger biopolymer.